Idiopathic pulmonary fibrosis is a disease of unknown etiology characterized pathologically by a chronic inflammatory process that precedes and likely controls the alterations in connective tissue matrix that eventually destroys the normal lung architecture. The mechanisms involved in this process are not known but a complex cell-cell interactive sequence, involving principally neutrophils, lymphocytes, macrophages and fibroblast is believed to be responsible. The long-term objectives of this project are to determine what alterations in cellular composition, function and trafficking occurs in the lung parenchyma of patients with idiopathic pulmonary fibrosis and to relate these alterations to the disease stage, prognosis, and therapeutic responsiveness. Our specific aims are to: (1) correlate noninvasive methods, primarily bronchoalveolar lavage and a new lung scanning technique, Inulin- labelled neutrophils (or monocytes), with clinical and morphological parameters to determine if (and how) these methods are to be used in diagnosis, staging and predicting therapeutic response; (2) to utilize functional assays and immunohistochemical techniques to characterize the cells and extracellular matrix of the lung parenchyma and to correlate these findings with those obtained by BAL and with the clinical parameter. We expect that these investigations will answer several questions: What are the features of IPF that determine disease activity and therapeutic responsiveness? Is lavage analysis a sensitive and specific method for the detection of these features in all patients with IPF? How can lavage be used most effectively, especially its relationship to other measures of disease activity such as immune complexes? Is the inflammatory response in the lavage "in phase" with that found in the lung parenchyma? Can the extent and severity of the disease be measured/assessed by semiquantitative routine histologic methods or does it require morphometric techniques?